Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid β protein (Aβ) peptide "oligomers" and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Aβ assembly and protects neuronal cells from the toxic effect of soluble Aβ oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Aβ deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Aβ accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:26296 |
| Date | January 2008 |
| Creators | Bacher, Michael, Dodel, Richard, Aljabari, Bayan, Keyvani, Kathy, Marambaud, Phillippe, Kayed, Rakez, Glabe, Charles, Goertz, Nicole, Hoppmann, Anne, Sachser, Norbert, Klotsche, Jens, Schnell, Susanne, Lewejohann, Lars, Al-Abed, Yousef |
| Publisher | Rockefeller University Press |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Source | Journal of Experimental Medicine, 2008, Bd. 205, Nr. 7, S. 1593-1599, ISSN: 0022-1007, EISSN: 1540-9538 |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 10.1084/jem.20060467 |
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